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【结 构 式】 
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【药物名称】Regadenoson, CVT-3146, Lexiscan 【化学名称】2-[4-(N-Methylcarbamoyl)-1H-pyrazol-4-yl)adenosine 【CA登记号】313348-27-5 【 分 子 式 】C15H18N8O5 【 分 子 量 】390.36131 |
【开发单位】CV Therapeutics (Originator), Fujisawa (Licensee) 【药理作用】DIAGNOSTIC AGENTS, Adenosine A2A Agonists |
合成路线1
The condensation of 2-hydrazino adenosine (I) with (ethoxycarbonyl)malondialdehyde (II) generated the pyrazole ester (III). The target amide was then obtained by displacement of the ethyl ester group of (III) with an aqueous solution of methylamine at 65 C.
| 【1】 Zablocki, J.; et al.; 2-Substituted pi system derivatives of adenosine that are coronary vasodilators acting via the A2A adenosine receptor. Nucleosides Nucleotides Nucleic Acids 2001, 20, 4-7, 343. |
| 【2】 Zablocki, J.A.; Palle, V.P.; Elzein, E.O. (CV Therapeutics, Inc.); N-Pyrazole A2A receptor agonists. EP 1189916; US 6403567; WO 0078779 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 54960 | (2R,3R,4S,5R)-2-(6-amino-2-hydrazino-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol | C10H15N7O4 | 详情 | 详情 | |
| (II) | 28507 | ethyl 2-formyl-3-oxopropanoate | C6H8O4 | 详情 | 详情 | |
| (III) | 54961 | ethyl 1-{6-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-9H-purin-2-yl}-1H-pyrazole-4-carboxylate | C16H19N7O6 | 详情 | 详情 |
合成路线2
| 【1】 Schaeffer HJ, Thomas HJ. 1958. Synthesis of potential anticancer agents XIV. Ribosides of 2,6-disubstituted purines. J Am Chem Soc, 80: 3738～3741. |
| 【2】 Zablocki J, Elzein E. 2007. Process for preparaing an A2A-adenosine receptor agonist and its polymorphs. WO 2007/092372A1 (CV Therapeutics Inc). |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 25254 | 2,6-dichloro-9H-purine | 5451-40-1 | C5H2Cl2N4 | 详情 | 详情 |
| (III) | 67380 | (2R,3R,4R,5R)-2-acetoxy-5-((benzoyloxy)methyl)tetrahydrofuran-3,4-diyl dibenzoate | 14215-97-5 | C28H24O9 | 详情 | 详情 |
| (IV) | 67381 | (2R,3R,4R,5R)-2-((benzoyloxy)methyl)-5-chlorotetrahydrofuran-3,4-diyl dibenzoate | C26H21ClO7 | 详情 | 详情 | |
| (V) | 32565 | (2R,3R,4R,5R)-4-(benzoyloxy)-2-[(benzoyloxy)methyl]-5-(2,6-dichloro-9H-purin-9-yl)tetrahydro-3-furanyl benzoate | C31H22Cl2N4O7 | 详情 | 详情 | |
| (VI) | 67382 | (3R,4R,5R)-2-(2,6-dichloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol | 13276-52-3 | C10H10Cl2N4O4 | 详情 | 详情 |
| (VII) | 54960 | (2R,3R,4S,5R)-2-(6-amino-2-hydrazino-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol | C10H15N7O4 | 详情 | 详情 | |
| (VIII) | 67383 | ethyl 1-(9-((3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-6-(((E)-3-ethoxy-2-formyl-3-oxoprop-1-en-1-yl)amino)-9H-purin-2-yl)-1H-pyrazole-4-carboxylate | C22H25N7O9 | 详情 | 详情 |
Extended Information